GluN2A

Milestone represents initiation of first-ever clinical trial using NR2B-negative allosteric modulator to treat GRIN-related disorders NEW YORK--(BUSINESS WIRE)-- GRIN Therapeutics Inc., a leader in development of therapies to treat GRIN-related disorders, today announced that the first patient has been dosed in the Honeycomb Study, the Company’s Phase 1B clinical trial of radiprodil, an investigational NR2B-negative allosteric modulator in development for the treatment of GRIN-related disorders. Radiprodil targets the hyperactive receptors associated with the development and progression of GRIN-related disorders by potently and selectively modulating the Nmethyl-D-aspartate (NMDA) receptor subtype 2B (NR2B). “GRIN-related disorders represent a significant area of unmet need in healthcare and the initiation of the Honeycomb Study is a historic milestone for GRIN Therapeutics and for patients around the world who are in desperate need of new treatments,” said Michael A. Panzara, M.D., MPH, chief medical officer of Neurvati Neurosciences, the parent company of GRIN Therapeutics. “We continue to be inspired by the children and families affected by GRIN-related disorders and by the leaders from the treatment community who have supported this important research and are very grateful for their partnership.” GRIN-related disorders are genetically defined, rare pediatric developmental and epileptic encephalopathies (DEEs) caused by mutations in the gene coding on the NMDA glutamate receptor. People living with GRIN-related disorders present with a spectrum of symptoms including epilepsy, behavioral disorders, autism, intellectual disability, and movement disorders. Currently, there are no disease-specific treatment options for GRIN-related disorders. Radiprodil is a small molecule that selectively targets NR2B-NMDA receptors that are overactive in GRIN-related disorders and that represent important potential targets in effective therapeutic intervention. “When we identified the genes that cause GRIN-related disorders in 2014, we never imagined the collaboration that would be undertaken to get into the clinic so quickly,” stated Johannes Lemke, M.D., Head of Leipzig University Hospitals' Institute of Human Genetics. “Working together with GRIN Therapeutics to evaluate radiprodil in patients with GRIN-related disorders represents an important advancement and I look forward to the study results with anticipation and optimism.” The open label Honeycomb phase 1B study will evaluate the safety, tolerability, pharmacokinetics, and effects on seizures, behavioral symptoms, sleep, and motor functions of multiple individually titrated doses of radiprodil in children with GRIN-related disorders. The trial will include up to 24 participants between the ages of six months and 12 years with confirmed gain-of-function (GoF) variants causing GRIN-related disorders, including variants on GRIN2B, GRIN2A, GRIN2D, and GRIN1. The trial will include one cohort of patients who have experienced drug resistant seizures with a frequency of at least once weekly and a second cohort including patients with behavioral and other symptoms who have experienced fewer or no seizures. The study will consist of a screening period, a titration period, and a maintenance period on the highest tolerated dose. Upon completion of treatment, participants will have the option to enter a long-term extension study. About Radiprodil: Radiprodil is an investigational, selective negative allosteric modulator of the Nmethyl-D-aspartate receptor subtype 2B (NR2B). It has been shown to inhibit NMDA glutamate currents when tested using receptors containing NR2B subunits coded by gain of function (GoF) mutations in the GRIN2B and GRIN2A genes, which are known to cause GRIN-related disorders. (Mullier et al 2017; Han et al 2021). About GRIN Therapeutics: GRIN Therapeutics is a life sciences company working to develop the investigational product radiprodil as a novel therapy for patients diagnosed with GRIN-related disorders. The company has initiated the Honeycomb phase 1 clinical trial to assess the safety and efficacy of radiprodil in the treatment of GRIN-related disorders. About Neurvati Neurosciences Neurvati Neurosciences is a Blackstone Life Sciences portfolio company established to advance development of high-potential technologies to address a broad range of unmet needs in the treatment of neurological and psychiatric disorders. Neurvati’s collaborative model supports rapid late-stage development of innovative treatments supported by robust pre-clinical and clinical data across the neuroscience landscape to improve the lives of patients. The Neurvati team is driven by a deep understanding of all phases of drug development and the regulatory and commercialization processes associated with therapies to treat brain and nervous system diseases. For more information, please visit neurvati.com.

Neumora Therapeutics has made some changes to its pipeline since it burst onto the scene one year ago. One year after its splashy $500 million unveiling, Neumora Therapeutics is back with a series B to keep its multiprogram neuroscience pipeline moving toward and through the clinic. The series B syndicate has put up $112 million, a sum that is big by most standards but dwarfed by the biotech’s first round. Neumora has raised around $650 million to date to test the idea that the precision medicine advances that have transformed oncology are now ready to redefine how neurological diseases are treated. As has happened in cancer, neuroscience could shift from a broad-brush approach that has lackluster outcomes because of patient heterogeneity to a more targeted paradigm that zeros in on likely responders. Arch Venture Partners led the series A, which included a $100 million investment from Amgen. Both Arch and Amgen have returned for the series B, joining with fellow existing investors including F-Prime Capital and Invus and new backers such as Abu Dhabi Growth Fund to funnel $112 million into Neumora. The money will support the development of a pipeline that is led by NMRA-140, a KOR antagonist in phase 2 development as a treatment for depression. Neumora completed a 204-patient phase 2a trial of the candidate in adults with major depressive disorder and symptoms of anhedonia, the inability to feel pleasure in normally pleasurable activities, over the summer.  Neumora has made some changes to its pipeline since it burst onto the scene one year ago. In February, the biotech struck a deal with Vanderbilt University to secure global rights to a M4 muscarinic receptor positive allosteric modulator program. The program, now called NMRA-M4R, is one of two projects that are closing in on the clinic.  The neuroscience startup has also removed two programs from its pipeline, including one that was listed as its third most advanced project at the time of the series A. One year ago, NMRA-094, a drug designed to treat sleep disorders by acting on histamine and serotonin receptors, was moving through preclinical. The candidate is now absent from Neumora’s publicly disclosed pipeline.  NMRA-094 is joined on the cutting-room floor by NMRA-GRIN2B, which Neumora previously listed as a discovery-stage treatment for neuropsychiatric disorders. The biotech is continuing to develop a therapy designed to act on GRIN2A.